This application is a proposal for the investigation of lung microvascular filtration by the direct micropuncture technique. Two general aims govern this proposal: first, to determine whether filtration varies longitudinally along the microvascular tree, second, to quantify hydraulic conductance and macromulecular flux across the single lung microvessel. A major new experiment concerns determination of transmicrovascular liquid flux in single lung microvessels. We will modify the split-drop technique to directly characterize filtration and sieving in single 30 Mum arterioles and venules to determine the effects of intravascular protein content, macromolecular change and mediators on microvascular liquid flux. We will continue to use the whole organ approach with which we will characterize filtration as a function of vascular pressure in extra-alveolar vessels of dog and sheep lungs. For the first time, we will make microvascular pressure measurements in the intact dog lung. In the excised dog lung, we will compare microvascular pressures measured by the micropuncture, the occlusion and the isogravimetric techniques. In addition, we plan to determine the effects of blood flow and of several mediators on the microvascular pressure profile. To characterize the pressure-flow profile of the subpleural microcirculation, each measurement of microvascular pressure will be accompanied by a measurement of microvascular blood velocity. With regard to interstitial liquid pressure, we will determine the arterio-venous distribution, and the effects of lung inflation. Using chemical analyses of nanoliter volumes of interstitial fluid directly sampled by micropuncture, we will explore interstitial liquid protein composition to compute interstitial protein osmotic pressure and to determine the profile of interstitial macromolecular sieving. Using our combined data we will estimate membrane coefficients which quantify microvascular flux of water and macromolecules. We will continue to develop a complex, multi-segmental model of liquid and solute exchange incorporating regional heterogeneities. The results of our investigations will elucidate fundamental mechanisms in the regional control of lung microvascular permeability and will promote our understanding of the fundamental processes of pulmonary edema.